Cardiovascular tissue regeneration system based on multiscale scaffolds comprising double-layered hydrogels and fibers

Abstract

We report a technique to reconstruct cardiovascular tissue using multiscale scaffolds incorporating polycaprolactone fibers with double-layered hydrogels comprising fibrin hydrogel surrounded by secondary alginate hydrogel. The scaffolds compartmentalized cells into the core region of cardiac tissue and the peripheral region of blood vessels to construct cardiovascular tissue, which was accomplished by a triple culture system of adipose-derived mesenchymal stem cells (ADSCs) with C2C12 myoblasts on polycaprolactone (PCL) fibers along with human umbilical vein endothelial cells (HUVECs) in fibrin hydrogel. The secondary alginate hydrogel prevented encapsulated cells from migrating outside scaffold and maintained the scaffold structure without distortion after subcutaneous implantation. According to in vitro studies, resultant scaffolds promoted new blood vessel formation as well as cardiomyogenic phenotype expression of ADSCs. Cardiac muscle-specific genes were expressed from stem cells and peripheral blood vessels from HUVECs were also successfully developed in subcutaneously implanted cell-laden multiscale scaffolds. Furthermore, the encapsulated stem cells modulated the immune response of scaffolds by secreting anti-inflammatory cytokines for successful tissue construction. Our study reveals that multiscale scaffolds can be promising for the remodeling and transplantation of cardiovascular tissue.

Current Applications of Polycaprolactone as a Scaffold Material for Heart Regeneration

“…Because of this, there is an increase in cross-sectional area without additional mechanical reinforcement, resulting in the Young’s modulus of many scaffolds being over 100 times less than that of the bulk polymer . Additionally, a hydrogel is often used to embed these scaffolds and enhance cell proliferation. ,, The hydrogel increases overall cross-sectional area and thus can further decrease the effective Young’s modulus of the tissue . An in-depth discussion on fabrication methods and their implications is provided below.…”

“…PCL has been most extensively studied in bone tissue engineering applications for its stiff mechanical properties . Because the polymer gained FDA approval, more recent studies have incorporated PCL into engineered soft tissues such as the myocardium, where it has been found to promote structural integrity as well as CM proliferation, alignment, and maturation in both in vitro and in vivo studies. ,− It is often used in conjunction with other less rigid polymers and materials in order to enhance mechanical biomimicry of the native myocardium. ,, …”

Current Strategies for the Regeneration of Skeletal Muscle Tissue

“…The major limitations are typically weaker cell adhesion compared to hydrogels based on natural polymers and the risk of the stimulation of a foreign body reaction by the polymer or its degradation products [2,124]. Synthetic polymers such as poly-L-lactic acid (PLLA) [155,156], poly(lactic-co-glycolic acid) (PLGA) [156], PCL [157][158][159][160], poly(ethylene glycol) (PEG) [161][162][163] and their copolymers [164], and various polyurethanes (PU) [165][166][167][168] are preferred for musculoskeletal tissue engineering. Among the synthetic polymers, elastomers, such as polydimethylsiloxane (PDMS), have been extensively used for the 2D fabrication of tissue-engineered muscle thin films due to their excellent biostability and tunable elasticity [169,170].…”

Crosslinking Trends in Multicomponent Hydrogels for Biomedical Applications

“…[43][44][45][46][47][48] In recent years, the medical field has attracted projects towards the formulations of innovative hybrid-hydrogels with a synergistic combination of natural and biocompatible synthetic polymers, with the aim to protect the environment from harmful chemicals and reduce production-costs, which indirectly affect human life. Since hydrogels are used in a range of biomedical applications, such as: tissue engineering, [49] wound healing, [50,51] drug carriers, [52] cancer treatments, [53,54] etc., the gels produced, usually come directly into contact with tissues, blood vessels, internal organs, and as such, can affect the human body in many ways. Often, it can be difficult to employ these hydrogels directly in the human body, especially when the formation, properties and the degradation protocols of these materials have not been properly understood.…”